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Phosphorus Control
Table 1: Existing Oral Phosphate-binders
potentially promising phosphate binder, although no further
development has occurred.
• Aluminium carbonate and hydroxide
• Calcium carbonate and acetate
Nicotinamide is not really a phosphate-binder, but an inhibitor of sodium-
• Magnesium carbonate and hydroxide
dependent phosphate co-transport in the small intestine. It has been
• Calcium ketoglutarate
found to be effective in reducing hyperphosphataemia at a mean dose of
• Calcium alginate
• Zirconyl chloride
1,000mg (i.e. two tablets) compared with calcium carbonate. It is a cheap
• Nicotinamide
medication that is non-reimbursable in most countries, but long-term
• Poly (allamine hydrochloride) (Sevelamer, Renagel
®
) experience is lacking.
29
• Lanthanum carbonate (Fosrenol
®
)
Sevelamer hydrochloride (Renagel) is a non-calcium-, non-metal-based
Table 2: Daily Cost of Phosphate-binders
phosphate-binding polymer. It is a cross-linked poly (allylamine) that
forms ionic and – to a lesser extent – hydrogen bonds with phosphate
Agent Daily cost (£) and is completely resistant to digestive degradation and, therefore, not
Calcium acetate (3–6 tablets) 0.33–0.66
absorbed from the gastrointestinal tract.
30
As a binder, it is at least as
Titralac (6–40 tablets) 0.1–0.62
effective as calcium acetate, but, because of its structure, also binds
Calcichew (3–6 tablets) 0.3–0.61
certain fat-soluble vitamins such as 1,25 dihydroxyvitamin D
3
and
Calcichew Forte (3–6 tablets) 0.66–1.3
vitamin K.
31
Studies demonstrate a significant decrease in phosphate
Calcium 500 (3–6 tablets) 0.3–0.61
Calcidrink granules (1 sachet) 0.91
levels with an associated decrease in PTH. In 172 haemodialysis patients
Aluminium hydroxide (4–20 capsules) 0.24–1.18
treated for eight weeks, serum phosphate level was effectively
Sevelamer 800mg (8 capsules) 5.46 controlled and serum total cholesterol was lowered, all without the
Fosrenol 750mg (3 tablets) 5.07 induction of hypercalcaemia.
32
Also, it was shown that its use slowed
the progression of – or even arrested – coronary and aortic calcifications
osteomalacia, bone and muscle pain, iron-resistant microcytic anaemia compared with the administration of calcium carbonate or acetate.
33
and neurological abnormalities. Bone, brain, heart and liver are the Long-term studies confirmed that sevelamer is effective in lowering
major sites of aluminium deposition in the body, but the degree of serum phosphate levels in haemodialysis patients with a corresponding
aluminium retention does not correspond with the plasma level; reduction in calcium x phosphate product, and that the beneficial effect
therefore, the desferroxamine test is often used.
23
Aluminium may be
especially toxic in high-risk conditions such as postparathyroidectomy,
diabetes, low turnover bone states and following reinstitution of
dialysis after kidney transplantation.
24
Therefore, aluminium-containing
…the best phosphate binder is still the
phosphate binders may be considered in some treatment-resistant
one that the patient will take, so
cases, but only for short time periods or in patients with very short life
expectancy.
potency and pill burden are perhaps
the most important considerations.
Low doses of magnesium hydroxide or carbonate have been used in
place of, or in association with, calcium salts for the control of plasma
phosphate levels. Low-dose magnesium treatment is accompanied by
only slight increases in plasma magnesium concentrations and does not was sustained over time, but diarrhoea (16%) and pain (13%) were seen
appear to have any long-term deleterious effects on bone mineralisation. in phase III crossover studies.
34
Also, one safety consideration with
Higher doses should not be used since they frequently lead to diarrhoea sevelamer is its potential to decrease plasma carbonate levels and
and favour the occurrence of hyperkalaemia.
25
therefore exacerbate metabolic acidosis.
35
Data from two recent
mortality trials, Dialysis Clinical Outcomes Revisited (DCOR) and RIND,
Polyuronic acid derivatives, such as sodium ferrus citrate and have shown a survival benefit for patients treated with sevelamer versus
ferrihydride, have a significant capacity for absorbing phosphate. They those treated with CCBP.
36,37
Sevelamer is more expensive than
are only slightly soluble in the gastrointestinal tract and thus prevent conventional binders, which has limited its prescription in some
excessive uptake of iron, which makes them good candidates for countries and increases the cost of dialysis.
38
phosphate-binding. In a study by Ritz et al., there was a median
percentage decrease in serum phosphate of 20%, with a concomitant Lanthanum carbonate (Fosrenol) is a rare Earth element that has recently
decrease in urinary phosphate excretion; altered bowel habit was the been launched for the treatment of hyperphosphataemia in patients with
only reported side effect.
26
The use of cross-linked iron dextran has been end-stage renal disease (ESRD). Lanthanum carbonate binds phosphate
reported in haemodialysis patients. An added advantage may result optimally at pH 3–5, while retaining good binding activity across the full
from the small amount of iron absorbed by these often chronically iron- range of pH 1–7. The relative efficacy of lanthanum carbonate was
deficient patients.
27
compared with aluminium hydroxide, calcium carbonate and sevelamer
in a 5/6 nephrectomised rat model, with urinary phosphate measurement
Zirconyl chloride octahydrate has been evaluated as a dietary phosphate- as a surrogate for potency of phosphate binding. It was found that
binder in rats, in which it was as effective as aluminium chloride and lanthanum carbonate reduced urinary phosphate to the same extent as
reduced bone phosphate burden significantly.
28
This compound is a aluminium and more effectively than calcium carbonate or sevelamer.
39
32 EUROPEAN RENAL DISEASE 2007
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